The long term aid of this proposal is to delineate and characterize the mechanisms involved in maintaining blood flow and glomerular filtration rate constant in the face of alterations in arterial pressure. Since renal function is critically dependent on its microcirculation, understanding of the mechanisms which contribute to microvascular control of renal function at a single nephron level is of substantial interest. Emphasis will be placed on establishing the role of the tubuloglomerular feedback mechanism and the myogenic response in autoregulatory phenomena. Both mechanisms have been previously suggested as important determinants of autoregulatory efficacy; however, quantitative contributions of each mechanism to the autoregulatory response have not been clearly established. Using a recently developed in vitro preparation that involves perfusion of individual juxtamedullary nephrovascular units from rats with homologous blood, the microvasculature of the kidney can be clearly visualized. Videmoetric techniques will be utilized to evaluate the blood flow and segmental vascular diameter changes which occur in response to alterations in perfusion pressure. Micropuncture methodology will be used to measure hydrostatic pressure in the vasculature, as well as to evaluate the tubuloglomerular feedback-mediated changes in nephron function in response to altering tubular fluid flow. Experiments will be performed to characterize the autoregulatory response in vitro, to determine the myogenic capability of the vasculature, and to determine the sensitivity of the tubuloglomerular feedback system under these conditions. These experiments will set the basis for studies designed to evaluate the relative contributions of myogenic and tubuloglomeruler feedback mechanisms to the autoregulatory response. Other studies will be performed to assess whether or not there is any interaction between tubuloglomerular feedback and myogenic influences on renal microvascular function. Finally, studies will be performed to establish the dependency of autoregulation upon a number of putative modulators of the tubuloglomerular feedback mechanism, and to investigate the influence of suggested auto regulatory mediators (histamine and adenosine) on the tubuloglomerular feedback loop. These studies will help delineate the interrelationship between autoregulatory, tubuloglomerular feedback, and myogenic systems involved in control of renal microvascular function.